In, for example, Cell Research (registered trademark) system approved by the U.S. Food and Drug Administration [FDA] as the CTC [circulating tumor cell] detection that is typical application for detecting rare cells, all cells contained in 7.5 mL of blood are examined, and when 5 or more CTC are found in the case of breast cancer or prostatic cancer or 3 or more CTC are found in the case of colorectal cancer, judgment as positive metastatic breast cancer, prostatic cancer or colorectal cancer is made.
Because the concentration of CTC in blood is extremely low, a high detection power is required for detecting CTC. In the first stage for the detection, it is important that rare cells such as CTC are made to appear in the detection area (e.g., observation visual field of microscope, or the like) with an extremely high probability.
As techniques for detecting cells, several techniques wherein cells are enclosed in a large number of microchambers are known. For example, in a patent literature 1, detection of malaria cells in blood is aimed, and in this detection, large amounts of erythroid cells are fed onto a chip equipped with microchambers each having a well structure, and the detection object is only the erythrocyte enclosed in the wells. FIG. 7 (FIG. 7 of the patent literature 1) shows that, in 3 kinds of microarray chips A to C each of which is equipped with microchambers having specific inner diameters and depths, erythroid cells are enclosed in the microchambers. In each chip, however, the space between the microchambers is large. On that account, it can be easily presumed that when a sample is simply fed onto the microarray chip, large amounts of cells remain outside the microchambers. In addition thereto, such microarray chips are disclosed in patent literatures 2 and 3 and a non patent literature 1.
For example, in the case where the degree of malignancy of breast cancer is intended to be judged from blood of a subject who has been diagnosed with breast cancer by the use of the microarray chip described in the patent literature 1, if 6 CTC are contained in 7.5 mL of the blood and if cells corresponding to 80% of all of the cells fed onto the surface of the microarray chip described in the patent literature 1 can be enclosed in the microchambers, the number of CTC enclosed in the microchambers is 4.8, namely, less than 5. According to the judgment by the Cell Research (registered trademark) system, it is judged to be “negative”, and “false negative” occurs.
By the way, when a microchamber type device is intended to be produced in view of industrial mass productivity, molding (or production) using a mold is generally carried out. As a means to improve a ratio of the number of cells enclosed in the microchambers to the number of all of the cells contained in the blood sample, namely, a recovery ratio of cells, a microchamber type device, in which the microchambers are arranged closely to each other, that is, the area outside the microchambers is minimized, can be also considered. However, if it is supposed to “remove” a microchamber type device from a mold during the production using a mold, such a microchamber type device is not realistic, and it is apparent that a certain degree of space becomes necessary between the microchambers.
In order to adopt such a microchamber type device to the detection of rare cells, it is necessary to develop a cell-spreading microchamber device in consideration of a high recovery ratio of cells and efficient mass productivity, namely, capability for production using a mold.